The goal of this proposal is to elucidate the structural and molecular substrates for intensity coding in the auditory system. The experiments are designed to determine how auditory receptors encode stimulus intensity, how the peripheral nerve fibers that convey the result of sensory transduction toward the brain are organized, how the central structures that receive these nerve fibers are arranged for the neural processing of loudness, and how the efferent nerves project from the central nervous system to the sensory hair cells in the cochlea. The long range goals are to determine if differences in receptor design and spatial arrangement in the auditory system and tactile system result in different protocols for intensity coding between the two systems or of the systems are essentially similar despite peripheral diversity. Experiments will test whether each inner hair cell, with its ensemble of radial afferent fibers, forms a functional unit for intensity coding. Functionally characterized and stained auditory nerve fibers will be traced from the hair cells to the cochlear nucleus to reveal the structural organization of information coding for intensity at the first auditory center in the brainstem. Exposures to noise will be used to investigate the effects of intensity of cochlear structure and function and the relationship of molecular changes in function. Efferent nerve fibers terminating in the cochlea will be traced to their cell bodies of origin on the same and/or opposite sides of the brain stem. The specific aims will be addressed with well established histological, biochemical and molecular biological techniques that are proven to work in this lab. Molecular probes and stains will be used to label and localize specific cytoskeletal components and cells. Selections of the structures and proteins to be studied is based on current knowledge of the peripheral auditory receptor organ and its central processes. Conventional light microcopy, laser scanning confocal microscopy and electron microscopy will be used to identify cells and cytoskeletal elements at the subcellular level. The results will provide a scientific rational for methods that can be used to prevent or diminish the adverse effects of noise trauma, to devise treatments and prosthetic devices to ameliorate partial or profound deafness.